In humans, studies that investigate links between serotonin and creatine supplementation find that 21 trained males, given creatine via 22.8g creatine monohydrate (20g creatine equivalent) with 35g glucose, relative to a placebo of 160g glucose, was found to reduce the perception of fatigue in hot endurance training, possibly secondary to serotonergic modulation, specifically attentuating the increase of serotonin seen with exercise (normally seen to hinder exercise capacity in the heat[233]) while possibly increasing dopaminergic activity (conversely seen to benefit activity in the heat[234]).[155]

The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight [6]. The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day [7].
In contrast to strongman or powerlifting competitions, where physical strength is paramount, or to Olympic weightlifting, where the main point is equally split between strength and technique, bodybuilding competitions typically emphasize condition, size, and symmetry. Different organizations emphasize particular aspects of competition, and sometimes have different categories in which to compete.

Some other cytokines and hormones may increase the receptor activity. These include growth hormone (GH) which acts upon the growth hormone receptor (GHR)[166][167] to stimulate c-Src[168][169] which directly increases the activity of the CrT via phosphorylation. This is known to occur with the 55kDa version of c-Src but not the 70kDa version and requires CD59 alongside c-Src.[170]
Pick a few key exercises that together train the whole body. Presses, chinups, rows, and squat and deadlift variations are the best choices (more on these in Rules #2 and #3). Write down how much weight you can currently do for 5–10 reps on each of them, and, over the next few months, work your way up to where you can either add 10–20 pounds to each of those lifts or do 3–5 more reps with the same weight. That’s how you force your body to grow.
If you’ve been training longer than 6–12 months, you can split your workouts into upper- and lower-body days. The most common setup is to train upper body one day and lower the next so that each area gets trained twice in one week. If you train four days per week, you can train upper body on Monday, lower Tuesday, rest Wednesday, and then do upper body again on Thursday, lower body on Friday, and then rest on the weekend.
Nutricost's BCAA packs a powerful punch when it comes to quality for the price. With 6 grams of L-Leucine, L-Isoleucine, and L-Valine in every serving, and 83 servings per bottle, each scoop equates to just 23 cents. These high quality branched chain amino acids help support protein synthesis, muscle recovery, while boosting endurance and stamina. This straight forward formula is free of calories and comes in several natural, easily mixed fruit flavors. Keep Reading »
Beach muscles and Olympic lifts draw more attention. But the many little stabilizer muscles around your shoulders, hips, and midsection — collectively the core — provide a strong foundation. Challenging the stability and mobility of these key muscles with medicine balls, physioballs, mini-bands, and rotational movements (lifting, chopping) pays huge dividends.
Rheumatoid arthritis. Early research shows that taking creatine by mouth daily increases lean muscle mass and may improve muscle strength, but does not improve physical functioning in adults with rheumatoid arthritis. In children, taking a specific supplement containing creatine and fatty acids twice daily for 30 days might reduce pain and swelling. But the effects of creatine alone are not clear.
Need the motivation to push past your comfort zone and squeeze out one more push-up or bicep curl? Sure, it helps to remember that you’ll get stronger, rock more toned muscles and rev your metabolism, thanks to all that added muscle mass. But if that wasn’t enough, now comes news that all that pump-itude (yes, that’s an SNL reference) has psychological benefits, too.
A big clue is digestion. He does occasional cleanses. (“There’s no planes that week,” he said. “And no judgment at home.”) The slightest change in a muscle, just a stripe in a striation, is noticed. And while Heath does most workouts alone, he has a trainer, Hany Rambod, who is based in California. They see each other about once a month. In between, Heath sends photos and receives workout and dietary advice in return.
A study showed that 100mg/kg creatine monohydrate daily over four months supplemented by boys with DMD is able to enhance handgrip strength in the dominant hand only (less than 10% increase) and increase whole-body lean mass. While the trend toward whole body strength reduction seen in placebo was ablated and there was no interaction with corticosteroids,[560] this study failed to find an influence on activities of daily living or lung function.[560] Elsewhere in children not on corticosteroids with DMD, supplementation of 5g creatine for eight weeks was confirmed to increase muscular phosphocreatine content[554] and according to a manual muscle test (MMT) there was a significant improvement in muscular function relative to placebo, with more parents reporting benefit with creatine (53.8%) relative to placebo (14%).[554]
Now, while all three are definitely beneficial to the process, I’d consider metabolic stress and muscular damage to be of secondary and tertiary importance, respectively. In addition, they are also things that will pretty much take care of themselves when implementing the workout guidelines and recommendations we’ve already covered (namely for volume, rep ranges, rest periods and exercise selection).
The synthesis of creatine (from guanidinoacetate via GAMT) also requires SAMe as a cofactor and is implicated in homocysteine production. While supplementation of guanidinoacetate at 0.36% (prior to SAMe) can increase homocysteine by up to 50% in rats, supplementation of creatine (0.4%) is able to suppress homocysteine by up to 25%, secondary to reducing creatine synthesis,[309] and has been replicated elsewhere with 2% of the rat diet, while a loading phase did not alter the benefits.[124]
Weight gain might be the most common side effect. “Creatine can cause your body to hold on to water by pulling fluid into your cells via osmosis,” says Bates. “It doesn't necessarily cause you to gain weight as fat, but it can increase edema, or water weight.” Also, muscle is denser than fat, so in some cases building muscle can increase body weight overall (even if you’re simultaneously burning fat).
Researchers have long been interested in how exercise improves cognitive thinking — and whether it can ward off dementia later in life. Now, a whole slew of new studies is comparing whether strength training affects the brain differently than cardio. One Italian study of 80 older people found that those who completed a 12-week strength regimen showed improved capacity for practical skills, whereas cardio training helped bolster them on analytic tasks. Researchers are still trying to understand the “why” behind this study — but so far, we’re impressed.
There is some research that suggests that creatine can help people with type 2 diabetes by improving insulin sensitivity, glucose uptake into the cells, and glycemic control. This has led many people with T2 to start supplementing their diets with pure creatine to try and reap the benefits. At this time there has been no conclusive research done into the effectiveness of creatine for type 1 diabetics.
The muscle strength objective is pursued when you want your muscles to be effective when a high number of repetitions will be involved, or in other words when you want your muscles to be strong for a continued period of time. You'll want to use approximately 4 sets from which 10-12 reps are performed. The muscle strength objective is often used for muscles located in your back and your abdominals.
Young adult athletes who reported creatine usage for over two years prior to the study (retrospective design) were not significantly different than controls.[501] Elsewhere, in a similar cohort of athletes reporting creatine usage for up to four years, failed to note significant differences in liver enzymes, although a nonsignificant reduction in LDH was noted.[502]
Using clinically effective doses of potent ingredients, Transparent Labs' StrengthSeries Creatine HMB combines creatine monohydrate with HMB in order to boost strength, lengthen endurance, and reduce fat. Along with the addition of BioPerine, StrengthSeries Creatine HMB is able to increase the rate of absorption and dispersion of this powerful creatine formula. Each serving of Creatine HMB contains 5g of Creatine, 2 g of HMB, and 5mg of BioPerine!	Keep Reading »

Taking high doses of creatine might harm the kidneys. Some medications can also harm the kidneys. Taking creatine with medications that can harm the kidneys might increase the chance of kidney damage.

Some of these medications that can harm the kidneys include cyclosporine (Neoral, Sandimmune); aminoglycosides including amikacin (Amikin), gentamicin (Garamycin, Gentak, others), and tobramycin (Nebcin, others); nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen (Advil, Motrin, Nuprin, others), indomethacin (Indocin), naproxen (Aleve, Anaprox, Naprelan, Naprosyn), piroxicam (Feldene); and numerous others.

Creatine pyruvate (also known as creatine 2-oxopropanoate) in an isomolar dose relative to creatine monohydrate has been shown to produce higher plasma levels of creatine (peak and AUC) with no discernible differences in absorption or excretion values.[83] The same study noted increased performance from creatine pyruvate at low (4.4g creatine equivalence) doses relative to citrate and monohydrate, possibly due to the pyruvate group.

Moving through repetitions too quickly, going too fast; there is nothing gained by lifting weights fast. Some of the perks of lifting weight in a slow and controlled manner, include more total muscle tension and force produced, more muscle-fiber activation both slow and fast twitch fibers, and less tissue trauma. Remember, a joint is only as strong as the muscles that cross it; if you haven't lifted in a long time, or ever, be careful what you ask of your joints.
Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].
A recent review article published in The American Journal of Clinical Nutrition highlighted the benefits of protein supplementation and showed that supplementing with protein during prolonged (greater than 6 weeks) resistance-type training can lead to significantly greater increases in muscle mass and strength when compared to resistance training without a dietary protein intervention.[15]
If you are doing this on your own, but are overwhelmed and confused about strength training, I know how that feels. It can be scary enough to keep MOST people from starting, which is actually why we created our 1-on-1 Coaching Program. Our coach gets to know you, builds a program based on your experience and goals, will check your form on each movement (via video), and keep you accountable and on track!

An upper/lower split can last you forever. A lot of massive, strong powerlifters stick with that throughout their entire lifting careers. However, if you’re older and/or have some trouble recovering, you may prefer a push/pull/legs split that has you training everything directly once per week. This is how most famous bodybuilders have trained in the past and many still do.
Great! Start with strength training 🙂 When you’re overweight, my guess is that you want to be preserving the muscle you have while losing the majority of your weight through fat. With strength training, your overall weight loss may seem slower, but you will lose inches faster. Strength training increases your metabolism; as long as you’re still eating in a deficit, you’ll lose weight.

A: Start with the calculations above but don’t be afraid to adjust up or down. Your metabolism and physiology will adapt to more food by trying to maintain homeostasis and regulate your bodyweight. Some may have to increase more than others but the number on the scale doesn’t lie. If it’s not going up, then you probably need to increase your calories.
Eating the right carbs is important too. Carbohydrate is stored in your body in the form of glycogen. Glycogen in the muscles is an important fuel reserve during intense physical exercise or in times of energy restriction – protein sparing. It is best to restrict or to keep away from junk carbohydrates such as sweets, cakes, and biscuits, and stick to foods like porridge, pasta (wholemeal), rice (brown), bread (wholegrain), and cereals (try to choose the versions with low or reduced sugar and salt). For more on carbohydrate and the effect of sugar on the body, click here.

However, the basis of “take creatine after your workout” comes from a 2013 study published in the JISSN, which can be found here (open access too!). In this study, recreational male bodybuilders (19 men overall) were given five grams of creatine either before or after their workouts. They trained five days per week but were also directed to consume 5g on their rest days at any time they wanted. The workouts were fairly similar to most gym workouts, and the methodology (what they did and how they did it) suggests that the findings would apply to most weightlifters.

The important role of nutrition in building muscle and losing fat means bodybuilders may consume a wide variety of dietary supplements.[41] Various products are used in an attempt to augment muscle size, increase the rate of fat loss, improve joint health, increase natural testosterone production, enhance training performance and prevent potential nutrient deficiencies.
The type of exercise performed also depends on the individual's goals. Those who seek to increase their performance in sports would focus mostly on compound exercises, with isolation exercises being used to strengthen just those muscles that are holding the athlete back. Similarly, a powerlifter would focus on the specific compound exercises that are performed at powerlifting competitions. However, those who seek to improve the look of their body without necessarily maximizing their strength gains (including bodybuilders) would put more of an emphasis on isolation exercises. Both types of athletes, however, generally make use of both compound and isolation exercises.
Brain injury. Early research shows that taking creatine by mouth daily for 7 days increases the ability to exercise by increasing lung function in people with a spinal cord injury. However, other research shows that creatine does not improve wrist muscle or hand function. Early research also shows that taking creatine by mouth daily for 6 months reduces amnesia following a traumatic brain injury in children.
Naturally produced in the kidneys, pancreas and liver, creatine is transported to muscle tissue where it is transformed into creatine phosphate, from which the energy molecule ATP is produced to regenerate the muscles' ability to contract and generate power during short-burst (anaerobic) activity. This translates to more productive workouts and faster muscle growth.
Cyclocreatine appears to be passively diffused through membranes and not subject to the creatine transporter, which can be beneficial for cases where creatine transporter function is compromised (creatine non-response and SLG6A8 deficiency). Similar to other forms of creatine, it buffers ATP concentrations, although its efficacy as a supplement in otherwise healthy people is currently unknown.
3) Relatively low cholesterol. This is one nutrition category that many people overlook with these supplements, but it's arguable one of the most important. Remember, if you're going to be downing 2 of these a day, you DON'T want to be maxing out your cholesterol intake. Luckily, this whey keeps it down to 30mg per scoop (which is about 10% of your daily intake). I've seen worse and ... full review
One limitation of many free weight exercises and exercise machines is that the muscle is working maximally against gravity during only a small portion of the lift. Some exercise-specific machines feature an oval cam (first introduced by Nautilus) which varies the resistance, so that the resistance, and the muscle force required, remains constant throughout the full range of motion of the exercise.
It's OK to be a little sore. Your muscles might feel achy or tired the day after a tough training session thanks to DOMS, or delayed onset muscle soreness. When you strength train you're causing microscopic damage to the tissue that will be repaired, that's how you build stronger lean muscle. Speaking of repair and recovery, though, rest days are important. "If you constantly break down muscle without a recovery period, you won’t give the muscle fibers a chance to repair and build back stronger,” explains Davis.
If you are doing this on your own, but are overwhelmed and confused about strength training, I know how that feels. It can be scary enough to keep MOST people from starting, which is actually why we created our 1-on-1 Coaching Program. Our coach gets to know you, builds a program based on your experience and goals, will check your form on each movement (via video), and keep you accountable and on track!
2-4 Minutes Rest: Ideal for “tension exercises,” which includes most primary compound exercises. I personally take 3 minutes for the big stuff, sometimes going into the 3-4 minute range depending on exactly what I’m doing and what I feel like I need at the time. Since making strength gains is the main focus of these exercises, longer rest periods like this will be optimal for making it happen.
The general strategy adopted by most present-day competitive bodybuilders is to make muscle gains for most of the year (known as the "off-season") and, approximately 12–14 weeks from competition, lose a maximum of body fat (referred to as "cutting") while preserving as much muscular mass as possible. The bulking phase entails remaining in a net positive energy balance (calorie surplus). The amount of a surplus in which a person remains is based on the person's goals, as a bigger surplus and longer bulking phase will create more fat tissue. The surplus of calories relative to one's energy balance will ensure that muscles remain in a state of anabolism.

Creatine is known to occur in highly concetrated levels in chicken photoreceptors, relative to other parts of the eye (10-15mM[466]) alongside high levels of creatine kinase.[466] The creatine transporter in human eyes also seems to be concentrated in the photoreceptors,[468] which are known to be susceptible to hypoxic cellular death[471][472] which, for humans, usually means retinal detachment.[473]

To meet the demands of a high-intensity exercise, such as a sprint, muscles derive their energy from a series of reactions involving adenosine triphosphate (ATP), phosphocreatine (PCr), adenosine diphosphate (ADP), and creatine. ATP, the amount of which is relatively constant, provides energy when it releases a phosphate molecule and becomes ADP. ATP is regenerated when PCr donates a phosphate molecule that combines with ADP. Stored PCr can fuel the first 4-5 seconds of a sprint, but another fuel source must provide the energy to sustain the activity. Creatine supplements increase the storage of PCr, thus making more ATP available to fuel the working muscles and enable them to work harder before becoming fatigued [1].
This is another thing I am very tired of hearing. 'No matter what I do or what I eat, I can't gain weight'. I have heard this countless times and I am here to tell you that you are dead wrong. That's OK, because I actually said the same thing until I realized the truth. Most people think they are eating a lot and you just may be. But no matter what you are eating, if you are not gaining, you are not eating enough. Most times, you should re-evaluate your diet as well and focus on more calorie dense foods. But you need to eat more if you are not gaining.
Makes You Healthier: If you’re looking for a workout in which you get the biggest bang for your buck, strength training is it. Strength training increases bone density, builds a stronger heart, reduces your resting blood pressure, improves blood flow, halts muscle loss, helps control blood sugar, improves cholesterol levels, and improves your balance and coordination (turning you from this, to this).
Casein, the source of the white color of milk, accounts for 70-80% of milk protein. Casein exists in what’s known as a micelle, a compound similar to a soap sud which has a water-averse inside and water-loving outside. This property allows the protein to provide a sustained, slow release of amino acids into the blood stream, sometimes lasting for hours. This makes casein a good protein source immediately before a workout to provide a continual amino acid supply to the muscles. Some studies suggest that combined supplementation with casein and whey offers the greatest muscular strength improvement (Kerksick, 2006).

Vegetarians and other people who have lower total creatine levels when they start taking creatine supplements seem to get more benefit than people who start with a higher level of creatine. Skeletal muscle will only hold a certain amount of creatine; adding more won't raise levels any more. This "saturation point" is usually reached within the first few days of taking a "loading dose."
Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly).
Another favorite bodybuilding supplement, creatine is an amino acid found in the body. The highest levels of this molecule are in your muscles and brain. It is made by your liver, pancreas and kidneys, but is also found in foods including meat, eggs and fish. Research has shown that it may help athletes including weightlifters who need short bursts of energy (5). In this study, creatine monohydrate proved to be an effective muscle builder. It works to improve body composition, muscle mass, strength and power.  Note that it was also more effective than other forms of creatine. How does it do this?
There have also been concerns that creatine can cause kidney damage, and doctors warn that people with a history of kidney disease or conditions, such as diabetes, that increase the risk of kidney problems should steer clear of the supplement. Combining creatine with nephrotoxic drugs — drugs that might damage the kidneys — like nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (advil or motrin) and naproxen sodium (Aleve), should also be avoided, according to the U.S. Department of Health and Human Services. (1)

The creatine kinase (CK) enzyme in rat heart tissue appears to have a KM around 6mM of creatine as substrate.[280] and is known to positively influence mitochondrial function as higher cytoplasmic phosphocreatine concentrations (not so much creatine per se) increase the oxidative efficiency of mitochondria[280] This is thought to be due to the transfer of high energy phosphate groups.[280]

When you’re planning your high-protein meals, 20 grams of protein is the optimal amount generally accepted for muscle growth. Research has found that the body doesn’t use much more than 20 grams for muscle-building at any one sitting. Around 80 grams of protein per day (or, four meals containing 20-grams of protein each) is about right for most people.
Creatine is known to be present in the retina due to the expression of creatine kinase (CK)[466][39] and the GAMT enzyme of creatine synthesis, which is also present in the mammalian retina.[467] Creatine in the blood can be transported into the retina via the creatine transporter (confirmed in humans[468]), and inhibiting transporter activity (by depleting the medium of chloride and sodium) reduces uptake by 80%.[469] The fact that not all uptake was inhibited suggests that another transporter, such as the monocarboxylate transporter MCT12 (or SLC16A12),[470] plays a role, perhaps moreso in the lens, where its levels were comparable to that of the major creatine transporter SLC6A8.[470] 
In muscle cells, the creatine transporter is predominantly localized to the sarcolemmal membrane. Western blot analysis of creatine transporter expression revealed the presence of two distinc protein bands, migrating at 55kDa and 70kDa on reducing SDS-PAGE gels.[147][148] The 73kDa band has been reported to be the predominant band in humans, with no differences based on gender.[148] A more recent report demonstrated that the 55kDa creatine transporter variant is glycosylated, forming the 73 kDa protein. Therefore, the 55 and 75kDa protein bands are actually immature and mature/processed forms of the creatine transporter protein, respectively.[149]
AAKG β-hydroxy β-methylbutyrate Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine/Creatine supplements Dietary fiber Echinacea Elemental calcium Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Guarana Iron supplements Japanese Honeysuckle Krill oil Lingzhi Linseed oil Lipoic acid Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John's wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate
Weight training has also been shown to benefit dieters as it inhibits lean body mass loss (as opposed to fat loss) when under a caloric deficit. Weight training also strengthens bones, helping to prevent bone loss and osteoporosis. By increasing muscular strength and improving balance, weight training can also reduce falls by elderly persons. Weight training is also attracting attention for the benefits it can have on the brain, and in older adults, a 2017 meta analysis found that it was effective in improving cognitive performance.[38]

The benefits of weight training overall are comparable to most other types of strength training: increased muscle, tendon and ligament strength, bone density, flexibility, tone, metabolic rate, and postural support. This type of training will also help prevent injury for athletes. There are benefits and limitations to weight training as compared to other types of strength training. Contrary to popular belief, weight training can be beneficial for both men and women.
It’s perhaps best known for the aesthetic benefits. Creatine increases muscle size relatively quickly and while that’s in part due to an increase in muscle water content — a good thing, since it means we’re better hydrated — it does indeed appear to lead to actual hypertrophy over time. And bigger muscles aren’t just aesthetic: larger muscles can improve work capacity, explosiveness, fat oxidation, injury resilience, and recovery.
Even human studies can be misinterpreted or manipulated. A few years ago a then-esoteric trace mineral called boron was found to increase testosterone, but only in older women, as it turned out. When boron was tested in young men engaged in weight training, it proved worthless for increasing testosterone. That doesn't mean boron is useless; it helps the body use the minerals calcium and magnesium, and it appears to increase mental alertness.
The neuroprotective effects of creatine appear to exist in regard to dopamine biosynthesis, and the suppression of dopamine synthesis seen with some neurological toxins appears to be partially attenuated with dietary intake of creatine. The protective effect is weak to moderate in animal research, but appears to be additive with anti-inflammatories.
Bodybuilders also train small muscles with a similar volume, frequency and intensity of their larger muscles. Strength athletes laugh at this. “Curls are a waste of time” is a common phrase you will hear hurled at a bodybuilder. This is SILLY. Although big compound movements should be most people’s resistance training priority, smaller muscle group focus work has some benefits for every athlete. Bicep tears are quite common among strength athletes, especially strong men and powerlifters. This happens because these competitors will lift tremendous weights with their backs, but their biceps are the weak link. Many of these injuries could be prevented with some good old-fashioned bodybuilder type isolation work. If you are only as strong as your weak link, doesn’t it make sense to make those weak links strong ones?
Despite the popularity of creatine among young people, there has been very little research conducted in children under age 18. Of those studies, a few have suggested a positive effect but the overall evidence is inconclusive. In one study, teenage swimmers performed better after taking creatine; in another study, it helped high school soccer players sprint, dribble, and jump more effectively.
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[26] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.[27]